Transcranial stimulation with real-time monitoring

Abstract

Closed-loop transcranial stimulation and monitoring is disclosed that includes generating a stimulation signal having a set of first oscillation parameters; applying the stimulation signal transcranially to a patient; monitoring the stimulation signal as applied to the patient; receiving a brain activity signal from the patient; generating a feedback signal based on the monitored stimulation signal as applied to the patient; and generating a modified activity signal by subtracting the feedback signal from the brain activity signal; determining one or more second oscillation parameters of the modified activity signal; and adjusting the set of first oscillation parameters of the stimulation signal based on the one or more second oscillation parameters of the modified activity signal. Closed-loop transcranial stimulation and monitoring is also disclosed in which the patient is engaged in a cognitive task.

The invention claimed is: 
     
       1. A method of performing closed-loop transcranial stimulation comprising:
 generating, by using a processor, a stimulation signal having a set of first oscillation parameters; 
 applying, by using two or more electrodes, the stimulation signal transcranially to a patient; 
 monitoring, by using the processor, the stimulation signal as applied to the patient to determine changes in voltage and/or impedance of the stimulation signal for taking into account an actual nature of the stimulation signal; 
 engaging the patient in a cognitive task; 
 receiving, by using the processor, a brain activity signal from the patient; 
 generating, by using the processor, a feedback signal based on the monitored stimulation signal as applied to the patient; 
 generating, by using the processor, a modified activity signal by subtracting the feedback signal from the brain activity signal, wherein the subtraction of the feedback signal from the brain activity signal removes an artefact from the brain activity signal that is based on the stimulation signal; 
 iteratively optimizing the stimulation signal for a fit with the modified activity signal and triggering the application of the stimulation signal upon alignment of a phase of the stimulation signal with a phase of the modified activity signal; 
 determining, by using the processor, one or more second oscillation parameters of the generated modified activity signal; and 
 receiving, by using the processor, an external input to control how the stimulation signal is adjusted based on the one or more second oscillation parameters and/or to control which of the one or more second oscillation parameters of the modified activity signal, generated by subtracting the feedback signal constructed in view of the monitoring of the stimulation signal, from the brain activity signal, are determined and/or when the one or more second oscillation parameters are determined, wherein the external input is based on a response of the task provided to patient. 
 
     
     
       2. The method of  claim 1 , wherein the alignment of the phase of the stimulation signal with the phase of the modified activity signal comprises an in-phase alignment. 
     
     
       3. The method of  claim 1 , wherein the alignment of the phase of the stimulation signal with the phase of the modified activity signal comprises an anti-phase alignment. 
     
     
       4. The method of  claim 1 , wherein the stimulation signal comprises a transcranial alternating current signal (tACS) that is delivered in a constant current mode, wherein a voltage of the tACS signal varies due to changes in impedance. 
     
     
       5. The method of  claim 4 , wherein one or more properties of the stimulation signal as applied to the patient are monitored, such as the voltage and/or impedance of the stimulation signal as applied to the patient. 
     
     
       6. The method of  claim 1 , wherein the set of first oscillation parameters comprise a frequency, phase and/or amplitude of the stimulation signal. 
     
     
       7. The method of  claim 1 , wherein the one or more second oscillation parameters that are determined comprise any one or more of frequency, phase and amplitude of the modified activity signal. 
     
     
       8. The method of  claim 7 , wherein adjusting the set of first oscillation parameters comprising adjusting at least one of:
 a frequency of the stimulation signal to have the same frequency as the determined frequency of the modified activity signal; and 
 the phase of the stimulation signal to have the same phase as, or a desired phase-shift from, the determined phase of the modified activity signal. 
 
     
     
       9. The method of  claim 8 , wherein the phase of the stimulation signal is adjusted to have the same phase as the determined phase of the modified activity signal. 
     
     
       10. The method of  claim 7 , wherein adjusting the set of first oscillation parameters comprising adjusting the phase of the stimulation signal to have the same phase as, or a desired phase-shift from, the determined phase of the modified activity signal and adjusting a frequency of the stimulation signal to have the same frequency as the determined frequency of the modified activity signal. 
     
     
       11. The method of  claim 1 , wherein the brain activity signal and/or the modified activity signal is filtered into one or more frequency bands prior to determining the one or more second oscillation parameters, and wherein the stimulation signal comprises one or more frequency bands and adjusting the set of first oscillation parameters of the stimulation signal based on the one or more second oscillation parameters of the modified activity signal comprises adjusting the set of first oscillation parameters in at least one frequency band that corresponds to a frequency band in which the second oscillation parameters were determined. 
     
     
       12. The method of  claim 11 , wherein the frequency bands comprise one or more of: delta frequency band (<about 4 Hz), theta frequency band (about 4 to 8 Hz), alpha frequency band (about 8 to 14 Hz), beta frequency band (>about 14 Hz) and sub-bands and overlapping bands thereof, including gamma frequency band (>about 30 Hz) and Mu frequency band (about 8 to 12 Hz). 
     
     
       13. The method of  claim 1 , wherein the adjusting of the set of first oscillation parameters of the stimulation signal is based on a modulation parameter, in addition to the one or more second oscillation parameters that are determined, and wherein the modulation parameter is a chirp. 
     
     
       14. A method of performing closed-looped transcranial stimulation comprising:
 generating, by using a processor, a stimulation signal having a set of first oscillation parameters; 
 applying, by using two or more electrodes, the stimulation signal transcranially to a patient; 
 monitoring, by using the processor, the stimulation signal as applied to the patient to determine changes in voltage and/or impedance of the stimulation signal for taking into account an actual nature of the stimulation signal; 
 engaging the patient in a cognitive task: 
 receiving, by using the processor, a brain activity signal from the patient; 
 monitoring, by using the processor, a response of the patient to carrying out the task; 
 removing, by using the processor, an artefact from the brain activity signal that is based on the stimulation signal, to obtain a modified activity signal, wherein the removing of the artefact comprises determining a feedback signal and subtracting that feedback signal from the brain activity signal; 
 iteratively optimizing the stimulation signal for a fit with the modified activity signal and triggering the application of the stimulation signal upon alignment of a phase of the stimulation signal with a phase of the modified activity signal; 
 analysing, by using the processor, the modified activity signal and determining one or more second oscillation parameters; 
 receiving, by using the processor, an external input to control how the stimulation signal is adjusted based on the one or more second oscillation parameters and/or to control which of the one or more second oscillation parameters are determined and/or when the one or more second oscillation parameters of the modified activity signal, generated by subtracting the feedback signal constructed in view of the monitoring of the stimulation signal, from the brain activity signal, are determined, wherein the external input is based on a response of the task provided to the patient. 
 
     
     
       15. The method of  claim 14 , wherein the alignment of the phase of the stimulation signal with the phase of the modified activity signal comprises an in-phase alignment. 
     
     
       16. The method of  claim 14 , wherein the alignment of the phase of the stimulation signal with the phase of the modified activity signal comprises an anti-phase alignment. 
     
     
       17. The method of  claim 14 , wherein the monitoring of the response of the patient to carrying out the task is based at least partly on the analysis of the modified activity signal. 
     
     
       18. The method of  claim 14 , wherein the method comprises receiving task results derived from a particular behaviour or reaction of the patient to carrying out the task, and wherein the monitoring of the response of the patient to carrying out the task is based at least partly on an analysis of the task results. 
     
     
       19. The method of  claim 18 , wherein the task presented to the patient is modulated, at least in part, on the basis of the results of the task, and wherein the task presented to the patient is to be modulated, at least in part, on the basis of the analysis of the modified brain activity signal. 
     
     
       20. The method of  claim 14 , wherein the analysing the modified brain activity signal comprises determining which regions or anatomical sites of the patient's brain generated some or all components of the modified activity signal, and wherein the applying of the stimulation signal to the patient comprises applying the stimulation signal to one or more of the determined regions or anatomical sites.